Crucial steps in tumor progression and the process of metastasis, e.g. tumor growth, invasion through extracellular matrices and angiogenesis, involve proteolytic modification of the pericellular matrix surrounding tumor cells. A major class of proteases involved in these processes is the matrix metalloproteinases (MMPs), and inhibition of MMPs prevents progression and metastasis of several tumor types, including human breast carcinomas, in animal models. In vivo, tumor MMPs are usually produced by stromal cells associated with tumors rather than the tumor cells themselves. The tumor cell surface glycoprotein, EMMPRIN, stimulates MMP production by fibroblasts and endothelial cells, and may be an important regulator of MMP production during tumorigenesis in vivo. However no direct evidence for its role in tumor progression had been published prior to this study. The focus of this proposal has been to demonstrate directly whether or not EMMPRIN promotes breast cancer progression, whether a role for EMMPRIN in tumor progression may be to promote or induce angiogenesis, and whether approaches can be developed that may have future therapeutic potential. This study has shown that EMMPRIN promotes tumor growth and invasion in an animal model and that interference with the action of EMMPRIN may be an effective way to retard breast carcinoma progression in patients.